"BRCAness" syndrome in ovarian cancer: a case-control study describing the clinical features and outcome of patients with epithelial ovarian cancer associated with BRCA1 and BRCA2 mutations.
OBJECTIVE
We evaluated the clinical impact of germ-line BRCA1/2 mutations in patients with epithelial ovarian cancer (EOC) on responses to first and subsequent lines of chemotherapy, treatment-free interval (TFI) between each line of therapy, and overall survival (OS).


METHODS
Twenty-two EOC patients with germ-line BRCA1 or BRCA2 mutations (BRCA-positive) were selected from our database and matched (1:2) with 44 nonhereditary EOC controls (defined by no associated personal history of breast cancer and no family history of breast and ovarian cancer or an uninformative BRCA mutation test) for stage, histologic subtype, age, and year of diagnosis. All patients received primary platinum-based chemotherapy. Statistical comparisons included responses after first-, second-, and third-line treatment (chi(2)/Fisher's exact test) and median OS (Kaplan-Meier method/log-rank test).


RESULTS
Compared with controls, BRCA-positive patients had higher overall (95.5% v 59.1%; P = .002) and complete response rates (81.8% v 43.2%; P = .004) to first line treatment, higher responses to second and third line platinum-based chemotherapy (second line, 91.7% v 40.9% [P = .004]; third line, 100% v 14.3% [P = .005]) and longer TFIs. A significant improvement in median OS in BRCA-positive patients compared with controls was observed from both time of diagnosis (8.4 v 2.9 years; P < .002) and time of first relapse (5 v 1.6 years; P < .001). BRCA status, stage, and length of first response were independent prognostic factors from time of first relapse.


CONCLUSIONS
BRCA-positive EOC patients have better outcomes than nonhereditary EOC patients. There exists a clinical syndrome of BRCAness that includes serous histology, high response rates to first and subsequent lines of platinum-based treatment, longer TFIs between relapses, and improved OS.
Tan
David S P
DS
Gynaecological Oncology and Cancer Genetics Units, Royal Marsden Hospital, London, UK.
Rothermundt
Christian
C
Thomas
Karen
K
Bancroft
Elizabeth
E
Eeles
Rosalind
R
Shanley
Susan
S
Ardern-Jones
Audrey
A
Norman
Andrew
A
Kaye
Stanley B
SB
Gore
Martin E
ME
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D012008:Recurrence; D016896:Treatment Outcome
D000970:Antineoplastic Agents